Correlation Between Cystatin C And Contrast-induced Nephropathy After Cardiac Catheterization

Contrast-Induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI) is a serious complication of percutaneous coronary intervention (PCI) or contrast-enhanced CT. Contrast medium were given to twenty to thirty million people per year in China. According to the incidence of CIN of 1%-5%, about two hundred thousand to one million cases occured each year. Moreover, the use of contrast medium are growing at a rate of 20%-30% per year. Patients who develop CIN also have a significantly higher risk of mortality about 9.7 to 14%, longer hospital stays and more medical cost, leading to heavy burdens on the economy and society.However, the pathophysiological mechanism of CIN is still not completely clear. There is no effective treatment for CIN at present. Only the prevention of CIN in patients with coronary intervention were intensively researched. To early assess the risk of CIN before procedure and to explore the individual safe dose of contrast medium in coronary intervention become the key to prevent CIN.Several CI-AKI risk scores have been put forward so far, among which the Mehran scores is the most classical and commonly used one. This scores include eight major factors of CIN, such as age, diabetes mellitus and heart failure, etc. However, most of the previous risk scores are based on some qualitative risk factors, which are somehow subjective, like the NYH A classification of heart function. Simultaneously, since these risk scores are complicated, their usability in clinical practice is extremely limited. Therefore, it is necessary to find an objective, rapid and simple assessment tool to predict CI-AKI.Baseline creatinine clearance is considered one of the most important factors of CI-AKI. An estimated glomerular filtration rate was based on serum creatinine (sCr), using tools such as the Cockcroft-Gault equation, MDRD, etc. These equations usually include variables like age, weight and sex, which make it relatively complicated for screening high risk patients.Cystatin C is a 120-amino-acid basic protein that belongs to the cystatin superfamily of cysteine proteinase inhibitors. In humans, all nucleated cells produce cystatin C at a constant rate, and this is eliminated by glomerular filtration in the kidneys. Since it is not dependent on age, sex, race, or muscle mass, serum levels of cystatin C offer a more precise estimation of GFR than do serum creatinine levels. While its predictive value of CIN among patients undergoing cardiac catheterization remains unknown.The contrast medium volume used during coronary angiography or PCI has also been shown to affect CI-AKI epidemiology. Higher CM volume (CMV) has been shown to be associated with increased rates of CI-AKI. A contrast volume to estimated glomerular filtration rate (V/eGFR) is the most commonly used predictor of CIN. However, in previous studies, glomerular filtration rate (GFR) estimation in the ratio was based on serum creatinine (sCr), using tools such as the Cockcroft-Gault equation, MDRD, etc. Recently, cystatin C alone, or in combination with sCr, has been considered a feasible and accurate alternative to sCr for estimating GFR, which also better predicts death and end-stage renal disease. While whether a contrast volume to eGFR based on cystatin C (eGFRcys) has better predictive value of CIN in patients undergoing cardiac catheterization is unknown.Objective and significance:1. To investigate whether a preprocedure cystatin C has predictive value of CI-AKI and long-term prognosis. This may help clinical doctor early detect high risk patients of CIN.2. To investigate whether a contrast volume to estimated GFR based on cystatin C (V/eGFRcys) has better predictive value of CIN and long-term prognosis. This ratio may help clinical doctor to evaluate the safe contrast medium volume before the procedure.Methods:1. Research pattern:single center, prospective, observational2. Patient selection:Inclusion criteria:(1) 18 years of age or older; (2)diagnosed with stable angina pectoris,unstable angina, prior myocardial infraction or suspected coronary artery disease, who was prepared to undergo coronary angiography or coronary intervention; (3) signed the informed consent.Exclusion criteria:(1) without coronary interventional therapy or death during the procedure; (2) severe heart failure (cardiogenic shock or NYHA class Ⅳ); (3) with end-stage renal disease or previous renal transplantation; (4) exposure to contrast agents within 1 week before or 72 hours after intervention or acute infectious diseases; (5) of radioactive contrast allergy; (6) pregnant, lactating or malignant tumor or expected life of less than one year; (7) use of nonsteroidal anti-inflammatory drugs, aminoglycoside drugs, cyclosporine, cisplatin, etc. within 48h before the intervention and the whole research process.3. Collection and definition of observation index:Upon patient hospitalization, Cystatin C was measured within 24h before the procedure. SCr was assessed in all patients at hospital admission and on Days 1,2, and 3 after CAG or PCI. The eGFRcys was calculated by the 2012 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation:133xmin(SCysC/0.8,1)-0.499×max(SCysC/0.8,1)-1328×0.996Age (x0.932 if female).Coronary lesions and treatment, stent implantation, the type and dose of contrast agent, renal artery angiography, duration of surgery, the incidence of arrhythmia and treatment, IABP implants were recorded.4. End points:Major end points:(1)CI-AKI:defined as an increase in serum creatinine of≥0.3 mg/dL or≥50% over baseline within 48 to 72 hours after the administration of contrast medium.(2)CIN:defined as an increase in serum creatinine of=0.5 mg/dL over baseline within 48 to 72 hours after the administration of contrast medium.Secondary end points:(1) Renal replacement therapy and/or death from acute renal failure. (2)Major adverse clinical events included all-cause mortality, renal replacement therapy, nonfatal myocardial infarction, acute heart failure, and target vessel revascularization.Results:1. Preprocedure Cystatin C Predicts the Risk of CI-AKI and long-term prognosis after Cardiac Catheterization1195 consecutive patients who underwent PCI or CAG were eligible for the present study.41 patients were excluded in the statistical due to missing key values. The mean patient age was 63.23±10.47 years, and the mean sCr was 89.14±42.56 μmol/L. The incidence of CI-AKI was 3.6%(42 patients). Cystatin C was higher in the CI-AKI group than the non-CI-AKI group (1.76±1.05 VS 1.20±0.50mg/L, P<0.001). In the CI-AKI group, the patients were older, had poorer preprocedural renal, presence of more lesions, higher Mehran risk score, etc. than the non-CI-AKI group. ROC curve analysis showed that the area under the curve (AUC) for the cystatin C to predict CIN was 0.75. A cutoff level of>1.3mg/L was a discriminator for CIN with higher sensitivity and specificity (76.2% and 70.1%, respectively). There was no significant difference between cystatin C and Mehran (AUC,0.75 vs 0.76, P=0.874); however, the AUC of the cystatin C was higher than sCr (AUC,0.75 vs 0.62, P< 0.001). The univariate logistics regression analysis shows that a cystatin C>1.3mg/L was a significant predictor of CIN (OR=7.52,95% CI 3.65-15.47, P< 0.001). In the multivariate analysis, a cystatin C>1.3mg/L (OR=5.52,95% CI 2.43-15.52, P<0.001) remained an independent risk factor of CIN after adjusting for other potential risk factors. During our long-term follow-up (median period:2.26±0.53 years), the patients with a cystatin C>1.3mg/L were at a higher risk of all-cause mortality (P<0.001) and MACEs (P<0.001) than were the patients with a ratio of cystatin C<1.3mg/L, according to the log-rank analysis, and this difference was statistically significant. 2. Contrast Volume to Cystatin C-based Glomerular Filtration Ratio Predicts the Risk of Contrast-Induced Nephropathy and long-term prognosis after Cardiac Catheterization1195 consecutive patients who underwent PCI or CAG were eligible for the present study. The mean patient age was 63.28±10.42 years, the mean contrast volume was 119.88±66.67 mL, and the mean CrCl was 73.81±26.47 ml/min. The incidence of CIN was 1.6%(19 patients). In the CIN group, the patients were older and had poorer preprocedural renal and heart function. Based on the V/eGFRcys ratio, the quartiles divided the data of all patients into four equal parts as follows:Q1 (<0.97, n=299), Q2 (0.97-1.71, n=303), Q3 (1.71-2.75, n=294), and Q4 (>2.75, n=299). From Q1 to Q4, positive trends were seen in terms of increased age, higher preprocedural SCr levels, greater CM dosage, presence of more lesions, higher ratio of V/CrCl or V/MDRD, Mehran risk score, etc. Patients with higher V/eGFRcys also had higher risk of CIN. The incidence of CIN was significantly (P= 0.008) higher among Q4 patients (3.7%) in relation to the V/eGFRcys ratio than among patients in any other quartile (0.7%,0.7%, and 1.4% for Q1 through Q3, respectively). ROC curve analysis showed that the area under the curve (AUC) for the V/eGFRcys to predict CIN was 0.730. A cutoff level of >2.29 was a discriminator for CIN with higher sensitivity and specificity (68.4% and 66.9%, respectively). There was no significant difference between the V/CrCl, V/MDRD and V/eGFRcys (V/eGFRcys VS V/CrCl P=0.330, V/eGFRcys VS V/MDRD P= 0.112); however, the AUC of the V/eGFRcys was higher. The univariate logistics regression analysis shows that a V/eGFRcys ratio >2.29 was a significant predictor of CIN (OR= 4.38,95% CI 1.65-11.62, P=0.003). In the multivariate analysis, a V/eGFRcys ratio of >2.29 (OR= 2.93,95%CI 1.02-8.44, P= 0.047) remained an independent risk factor of CIN after adjusting for other potential risk factors. In our study, an increase in V/eGFRcys was associated with a higher rate of in-hospital stroke (P=0.029) and a greater risk of requiring IABP (P= 0.022), but it was not associated with in-hospital MACEs. During our long-term follow-up (median period:2.26±0.53 years), the patients with a ratio of V/eGFRcys>2.29 were at a higher risk of all-cause mortality (P= 0.005) and MACEs (P=0.024) than were the patients with a ratio of V/eGFRcys<2.29, according to the log-rank analysis, and this difference was statistically significant. Cox regression analysis indicated that the V/CrCl ratio>2.29 remained a significant risk factor for death after cardiac catheterization, even after adjusting for the baseline clinical variables (hazard ratio= 1.99,95% CI 1.08-3.69, P=0.028).Conclusions:1. A preprocedural cystatin C>1.3 mg/L was a good predictor of CI-AKI, which was not different from Mehran scores. Besides, it was also associated with increased in-hospital adverse events and long-term prognosis. Preoperative measurement of cystatin C can help clinicians to identify high-risk CI-AKI patients, so as to take preventive measures in advance.2. A V/eGFRcys>2.29 was a significant and independent predictor of CIN after cardiac catheterization. Patients with V/eGFRcys>2.29 also have poor long-term prognosis. This ratio may help clinicians determine the individual maximum safe contrast medium volume. Besides, after procedure, if the calculating V/eGFRcys is more than 2.29, it is suggested that the patients with a greater risk of CIN. Such patients can be given rescue hydration and renal toxicity of drugs should be avoided.